Tricyclic antidepressants updated on 07-01-2025

Language disorders/delay

id	Study   Auto Suarez (Controls unexposed, discontinuers), 2022Suarez (Controls unexposed, general pop), 2022Nulman (Controls unexposed, disease free), 2002Nulman - Fluoxetine (Controls exposed to Fluoxetine), 2002Simon (Controls exposed to SSRIs), 2002Simon (Controls unexposed, NOS), 2002	Lib. in paper	Exposition period  Auto during pregnancy (anytime or not specified)1st trimester2nd trimester3rd trimester2nd and/or 3rd trimesterthroughout pregnancyearly pregnancydays before deliverylate pregnancypreconception-onlypericonceptionalpreconceptional for kinetic reasonat least 1st trimester3 months (or more) before pregnancy or during pregnancy1st and 2nd trimester3 months or more before pregnancy or1st trimesterPaternal exp. genotoxic window only (0–3 months preconception)Paternal exposure: epigenetic window only (3–xxx months preconception)Paternal exposure: genotoxic/epigenetic window (0–xxx months preconception)Paternal exposure: other window	Study type  All studies Case control excluded Only case control	Control type    Auto unexposed (general population or NOS)unexposed, sickunexposed, disease freeexposed to other treatment, sicknot specifiedsiblingwhatever (meta-analysis)	Tags	OR 95%CI	x1/n1 x0/n0	no cases	no exposed	ROB	Ref.
S18247 R76563	Suarez (Controls unexposed, discontinuers), 2022	Developmental Speech or Language Disorder - ≥ 2 dates with ICD-9 Dx 315.3x (except 315.34) - At 1.5 years of age	2nd and/or 3rd trimester	retrospective cohort (claims database)	unexposed, sick	Adjustment: Yes Monotherapy: no or not specified Unexposed sick: recent illness/treatment (during or juste before pregnancy or treatment stopped in view of pregnancy)	0.93 [0.73;1.20]	163/4,307   194/5,710	357	4,307		ref
S18248 R76571	Suarez (Controls unexposed, general pop), 2022	Developmental Speech or Language Disorder - ≥ 2 dates with ICD-9 Dx 315.3x (except 315.34) - At 1.5 years of age	2nd and/or 3rd trimester	retrospective cohort (claims database)	unexposed (general population or NOS) excluded	Adjustment: Yes Monotherapy: no or not specified	1.08 [0.92;1.27] excluded (control group)	166/4,357   66,394/2,965,988	66,560	4,357		ref
S10954 R40803	Nulman (Controls unexposed, disease free), 2002	Language, Expression with the Reynell Developmental Language Scale at 15-71 months	throughout pregnancy	prospective cohort	unexposed, disease free	Adjustment: No extrapolated (cont. endpoint) Monotherapy: TCA only	0.61 [0.27;1.37]	-/45   -/34	-	45		ref
S10953 R40798	Nulman - Fluoxetine (Controls exposed to Fluoxetine), 2002	Language, Expression with the Reynell Developmental Language Scale at 15-71 months	throughout pregnancy	prospective cohort	exposed to other treatment, sick excluded	Adjustment: No extrapolated (cont. endpoint) Monotherapy: TCA only	0.42 [0.19;0.94] excluded (control group)	-/45   -/37	-	45		ref
S10935 R40683	Simon (Controls exposed to SSRIs), 2002	Speech delay (infants’ medical records) - unspecified age	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	exposed to other treatment, sick excluded	Adjustment: No Monotherapy: TCA only	0.88 [0.12;6.34] C excluded (control group)	2/209   2/185	4	209		ref
S10936 R40699	Simon (Controls unexposed, NOS), 2002	Speech delay (infants’ medical records) - unspecified age	during pregnancy (anytime or not specified)	retrospective cohort (claims database)	unexposed (general population or NOS)	Adjustment: No Matched Monotherapy: TCA only	1.00 [0.14;7.17]	2/209   2/209	4	209		ref
					Total	3 studies	0.90 [0.71;1.14]		361	4,561
x1: number of endpoints among exposed, n1: number of exposed; x0: number of endpoints among non exposed, n0: number of non exposed; C: calculated odds ratio from numbers of events and effectives

Forest plot

Sensitivity analysis

Publication bias and p-hacking diagnosis

Sub-groups analysis using all included studies

excluded 10953, 10935, 18248